Volume 11 · Issue 06 · 2019

Precision medicine advocates the idea that each individual's different genetic background, environmental factors, and lifestyle need to be considered when formulating prevention and treatment options for diseases. Although diabetes and tumors are the first diseases that need to realize precision medicine, compared with the field of tumors, diabetes is obviously lagging behind in the development of precision medicine, from diagnosis, classification to treatment. However, with the progress of science, new technologies and research methods are constantly emerging, especially the development of "omics", and we have also seen the dawn of precision medicine in the field of diabetes. This article combs out the progress of precision medicine in the field of diabetes from the prediction, diagnosis and classification of diabetes and its complications to treatment; And it is proposed that in order to truly realize the precision medicine of diabetes, we must focus on the integrity of the whole body. Only by comprehensively understanding the nature and laws of disease occurrence and progression, applying the concepts and means of precision medicine, and towards the integration of genetics-environment-lifestyle can we truly promote and promote the development of early intervention, early prevention and precise management of diabetes in the future.

Diabetes is a group of lifelong diseases caused by the long-term combination of genetic factors and environmental factors. However, it has been found that certain treatments can achieve "remission" in some patients with type 2 diabetes-that is, blood sugar can be restored to normal levels without medication and maintained for a period of time. With the advancement of research and the development of medical technology, more and more medical articles and reviews on diabetes intervention use the term "remission" as one of the outcomes of diabetes treatment. However, there are still some differences in the definition and criteria of remission of type 2 diabetes in domestic and foreign studies in terms of blood glucose value and the specific time of maintenance. This paper will summarize and analyze the methods, remission results and definitions of three types of interventions that have been proved to "alleviate" type 2 diabetes mellitus, so as to deepen the understanding of remission criteria and their significance.

Diabetes mellitus is a clinical metabolic syndrome with defect of insulin secretion or defect of insulin action as the main pathological changes, hyperglycemia as the main feature and many abnormalities. According to the previous classification methods, the common types of diabetes are type 2 diabetes and type 1 diabetes. However, the previous classification methods have limitations, and they often encounter classification and treatment difficulties in clinic. The latest cluster analysis method based on six variables in the world can classify adult-onset type 1 and type 2 diabetes from another angle. This method may be more instructive for clinical practice than the past classification methods, but there are some shortcomings, and a lot of related research still needs to be carried out in the future.

With the rapid development of blood glucose monitoring technology, various continuous glucose monitoring reports have emerged successively. Because of the different interpretation methods, it brings a lot of inconvenience to clinicians. ambulatory glucose profile (AGP) is a standardized glucose monitoring report consistently recommended by domestic and foreign guidelines. AGP mainly includes a summary of blood glucose indicators, total glucose profile and daily trend chart. Accurate interpretation of AGP can understand the stability of blood glucose, hyperglycemia and hypoglycemia levels of patients. This paper will explain the composition of dynamic glucose map, the significance of various parameters, and the analysis steps of the map, and recommend the "six-step method" to interpret AGP in clinical work, which is convenient for medical staff to better communicate with patients and help control blood glucose to reach the standard smoothly.

Diabetic foot is one of the main causes of disability and death of diabetic patients. Based on the principle of "Chinese practice, Chinese evidence and Chinese guidelines", the Diabetology Branch of Chinese Medical Association, together with the Infectious Diseases Branch of Chinese Medical Association, the Tissue Repair and Regeneration Branch and other multidisciplinary experts in related fields, jointly formulated this clinical guideline adapting to the current situation of diabetic foot in China, aiming at standardizing the prevention, diagnosis and treatment of diabetic foot in China. This guideline has the following features: (1) highlighting clinical practicality; (2) Chinese evidence fully incorporated in the field of diabetic foot; (3) Pay attention to early screening and management, emphasizing that prevention of diabetic foot is better than treatment; (4) Emphasize the importance of standardized and comprehensive management; (5) Emphasize the multidisciplinary collaborative diagnosis and treatment of diabetic foot. In addition, with reference to the requirements of the 2017 version of China's Type 2 Diabetes Prevention and Treatment Guidelines, key points and evidence levels have been added, and the evidence levels are divided into three levels: A, B and C according to evidence quality, clinical significance, universality and applicability. Grade A: Evidence based on multiple randomized clinical trials or meta-analyses. Grade B: Evidence based on a single randomized clinical trial or multiple non-randomized controlled studies. Grade C: Expert consensus opinion only and/or based on results from small-scale studies, retrospective studies, and registered studies.

To investigate the relationship between self-management and dietary pattern among adults patients with type 1 diabetes mellitus (T1DM) by a Chinese version of the Summary of Diabetes Self-Care Activities Measure scale (C-SDSCA) and a short food frequency questionnaire (FFQ).

C-SDSCA scale and FFQ were performed on 100 adult T1DM patients recruited from Guangdong T1DM Translational Medicine Study from April to October in 2018. According to the score of C-SDSCA scale, patients were divided into three groups by self-management: excellent, moderate and poor behaviors. Dietary pattern of the participants was classified as appropriate/inappropriate based on the results of FFQ. Differences between groups were comparedusing t-test,ANOVA test or chi-square test, when applicable. The effect of self-management behavior on dietary pattern was analyzed using multivariate logistic regression model.

In total, 100 patients responded and 93 provided eligible responses. The average score of C-SDSCA scale was 59%, while only 25.8% (24/93) of the subjects had appropriate dietary patterns. Compared with patients with appropriate dietary patterns, those with in appropriate ones had significantly elevated level of HbA_1c [(7.4±1.1)% vs (6.9±1.0)%, t=-2.08,P=0.04]. The scores of C-SDSCA were higher in the group of patients with appropriate diet patterns comparing to those with inappropriate ones (45.63±11.71 vs 35.03±11.73,t=3.81,P<0.01). In the group of excellent self-management behaviors,55.6% (10/18) patients had appropriate dietary patterns,but the ratio were only 22.0% (13/59) and 6.2% (1/16) in the groups with moderate and poor self-management behaviors,respectively. Results from logistic regression shows that deterioration in self-management level by one category was associated with a 4.78-fold increase in the risk of inappropriate dietary pattern (OR=4.78, 95%CI 1.71-13.34, P<0.01).

Current situation of self-managing behaviors and dietary patterns of adult patients with T1DM were not ideal. It was found that appropriate dietary pattern was associated with better glycemic control and better self-managing behaviors, indicating that more attention should be paid to diet education in patients who have poorer self-management behaviors.

To investigate whether umbilical cord mesenchymal stem cells (UC-MSCs) can exert kidney protection in diabetes rats through regulating autophagy.

Type 2 diabetes rats model was induced by a high-fat diet combined with a low dosage of streptozotocin (STZ) intraperitoneal injection. After successful modeling,those rats were fed with a high-fat diet for another eight weeks,and the control group (10) was given a normal chow diet. The treatment group (MSCs group, 10) was infused UC-MSCs (3×10⁶ suspended in 0.5 ml PBS) via tail vein once every two weeks, for a total of eight weeks of treatment. The diabetes control group (T2DM group, 10) was infused 0.5 ml PBS solution via tail vein and the control group did not receive any treatment at the same time. Random blood glucose and body weight were monitored every two weeks. One week after the fourth treatment, intraperitoneal glucose tolerance test (IPGTT) was performed in all rats, and later on they were sacrificed and their kidneys were collected for histopathological examinations and autophagy-related protein examinations. Data was measured using two independent sample mean t tests, one-way ANOVA and repeated measures analysis of variance.

Compared to T2DM group,random blood glucose decreased [(23.9±3.7) vs (28.7±2.1) mmol/L,t= 3.568, P<0.01], and glucose tolerance improved (t=3.07-6.64, P<0.01) in MSCs group. The pathological results showed that in the MSCs group the degree of glomerular sclerosis was reduced (P<0.01, t=17.28), the glomerular basement membrane thickening was relieved (P<0.01, t=12.00),and the degree of renal interstitial fibrosis was improved (P<0.01, t=2.83-17.28). Examinations of autophagy-related proteins showed that the MSCs group exhibited increased expression of LC3[(78.3±5.3)% vs (33.4±8.3)%, t=10.22,P<0.01] and reduced expression of P62[(24.1±4.2)% vs (93.3±4.9)%, t=24.13,P<0.01],which indicated that the level of autophagy in rat kidneys were significantly increased after MSCs infusion.

UC-MSCs therapy has the function of kidney protection and delay the development of diabetic nephropathy, which may be related to the enhancement of autophagy in renal tissues.

To assess body composition changes after short-term treatment of Graves′ disease (GD) with weight loss and its consequent effects on metabolism.

A total of 150 patients with GD (male/female=52/98) were included in this study who met the requirements with weight loss before treatment and weight gain over 3% after six months of treatment with anti-thyroid medication. Body weight, blood lipids, blood glucose, and blood pressure changes were recorded before and after 6-month therapy. Dual-energy X-ray absorptiometry (DEXA) was performed to measure fat and lean tissue mass of body, trunk, arms, legs and other areas. Comparisons were performed by paired t-test or Wilcoxon sign rank test. The correlation between body composition and metabolic parameters was analyzed by multiple linear regression.

After six months of treatment with anti-thyroid drugs, thyroid functions were significantly improved. In body composition, body fat mass(BF), female, trunk fat mass (TF), body lean mass (BL), appendicular lean mass (AL), BF/weight(%), and TF/weight (%) all increased significantly, while BL/weight (%) decreased significantly (t=-11.709-16.106, P<0.05). After adjustment for age, sex,body mass index, and the changes of thyroid function, it was found that BF/weight, TF/weight were positively correlated with oral glucose tolerance tests 2 h PG [β(95%CI)=0.195(0.038-0.352), 0.261(0.023--0.500)], and BL/weight were negatively associated with it [β(95%CI)=-0.177(-0.328--0.027)]. There was no association between body composition andfasting plasma glucose, glycated hemoglobin A_1c, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, systolic blood pressure, and diastolic blood pressure (all P>0.05).

Short-term changes in regional fat and lean mass are inversely correlated to the improvement of metabolism in hyperthyroidism, however no impact on overall glycometabolism improvement with correction of hyperthyroidism.

To observe the change of heart rate variability (HRV) during asymptomatic hypoglycemia in patients with type 2 diabetes.

A total of 42 patients with type 2 diabetes who treated with insulin were enrolled. Patients were monitored with continuous glucose monitoring System (CGMS) and dynamic electrocardiogram for 72 hours. Heart rate variability was analyzed by spectral analysis during asymptomatic hypoglycemia (glucose ≤3.9mmol/L) (minimum length of 20 min). Spectral analysis including short-time frequency domain and time domain. The high-frequency, low-frequency were normalized (HFnu, LFnu), and low-frequency to high-frequency ratio were calculated. Heart rate SDNN (all NN intervals), SDANN (standard deviation of the averages of NN intervals in all 5-minute segments of entire recording), RMSSD (the square root of the mean of the sum of the squares of differences between adjacent NN intervals) were used as a time domain measure of HRV. Equal durationwith normal glucose (glucose 5-10 mmol/L) at the same time period on a different day was chosen to serve as control for each hypoglycemia event. Paired t test was used for comparison.

Among 42 patients 32 experienced at least one episode of hypoglycemia. A total of 48 data were eligible for analysis, among which 36 were asymptomatic hypoglycemia at night. Compared with euglycemia state, patients with asymptomatic hypoglycemia had significantly lower HFnu [(37.68±15.57) vs (45.97±13.20) ms², P<0.01], whileLFnushoweda decreasing trend there was no significant difference [(52.36±17.71) vs (54.15±14.27) ms², P>0.05]. These patients also had higher low-frequency/high-frequency ratio (P<0.05). SDNN, SDANN, and RMSSD all decreased in asymptomatic hypoglycemia (all P<0.05).Pearson correlation analysis showed that the levels of hypoglycemia was positively correlated with SDNN (r=0.484, P<0.05). Further stratification was performed according to the degree of hypoglycemia. There were 20 clinically significant hypoglycemia episodes (glucose<3mmol/L), SDANN and RMSSD decreased moresignificantlycompared with euglycemia (P<0.01), and there was still decreased significant difference in HFnu (35.9±15.2 vs 42.3±12.5, t=-2.259, P<0.05).

Heart rate variability decreased in type 2 diabetes patients with asymptomatic hypoglycemia, indicating the loss of cardio protection of vagal nerve activity

To evaluate the relationship between PR interval prolongation and diabetic retinopathy (DR), diabetic kidney disease (DKD) and carotid intima-media thickness (CIMT).

A total of 857 inpatients with type 2 diabetes mellitus (T2DM), from May 2014 to March 2016 at the Department of Endocrinology and Metabolism of Xijing Hospital affiliated to the Fourth Military Medical University were selected and divided into two groups according to their electrocardiogram results: PR≤ 200 ms (Group 1, n=812) and PR>200 ms (Group 2,n=45). The demographic data and biochemical markers including the age, gender, diabetic duration, fasting blood glucose (FPG), blood lipid, albumin creatinine rate, glomerular filtration rate and the prevalence of DR, prevalence of DKD, prevalence of CIMT were compared and analyzed among two groups. Statistical comparisons were performed using the Student t test or Nonparametric Tests. Logistic regression analysis were used to study the influencing factors for PR interval prolongation.

The mean PR interval of all patients was (162±23) ms. The prevalence of DR and DKD in patients with PR>200 ms were significantly more than those in patients with PR≤200 ms (69% vs 39%, 46.7% vs 23.4%, χ²=15.75,12.44, all P<0.01). Logistic regression analysis showed that the risk of PR interval prolongation for T2DM patients with DR was 2.168 times higher than those with non-DR (OR=2.168, 95%CI 1.055-4.455, P<0.05), and the risk of PR interval prolongation for T2DM patients with DKD was 2.317 times higher than those with non-DKD (OR=2.317, 95%CI 1.160-4.628, P<0.05), PR interval length was not correlated with CIMT in T2DM patients.

PR interval length is positively correlated with DR, and DKD, but no correlated with CIMT in type 2 diabetic patients.

To establish a new standard for measurement islet autoantibodies by electrochemiluminescence (ECL) assay and to discuss its applications for type 1 diabetes mellitus (T1DM) prediction and diagnosis.

ECL assay was used to measure serum levels of glutamic acid decarboxylase antibody (GADA65), insulin autoantibody (IAA) and protein tyrosine phosphatase antibody (IA-2A) in 124 healthy volunteers, 180 T1DM patients, and 180 type 2 diabetes mellitus (T2DM) patients. Patients admitted in Sir Run Run Hospital, Nanjing Medical University from December 2016 to June 2018 with diagnosis of T1DM or T2DM were enrolled in the study. Healthy volunteers were recruited from students in Nanjing Medical University. The serum antibody level was represented as antibody index. The positive cut-off limit for each antibody was defined as 99% of the indicated antibody index from healthy volunteers. The chi-square test was used to analyze the positivity of GADA65, IAA, IA-2A of T1DM and T2DM patients detected by ECL method.

The cut-off points for GADA65, IAA and IA-2A were 0.047, 0.009 and 0.0029 respectively by ECL methods. The intra-assay coefficients of variation (CV) for GADA65, IAA and IA-2A were 1.88%-8.30%, 1.39%-3.40%, 1.23%-3.17% respectively, and the inter-assay CV were 3.9%-7.3%, 2.7%-9.8%, 2.2%-7.4% respectively. The repeatability of the result was 99.8%. The positivity of GADA65, IAA,IA-2A were 52% (94/180), 45% (81/180), 21% (39/180) respectively in T1DM patients and were 2.2% (4/180), 2.2% (4/180), 2.2% (4/180) respectively in T2DM patients. There were statistic significances in positivity between T1DM and T2DM for all three antibodies (χ²=113.57,32.35,91.31, all P<0.001). The positive ratio of GADA65 and IA-2A detected by ECL or radio-binding assay shows no difference.

The ECL assay has high sensitivity, specificity and repeatability and could be used for the prediction and diagnosis of T1DM.

Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes, especially chronic pain, numbness and autonomic dysfunction seriously reduce the quality of life of diabetic patients. The immunoregulatory, tissue repair and neurotrophic effects of mesenchymal stem cells (MSCs), especially umbilical cord mesenchymal stem cells, have attracted much attention in recent years. In this paper, we will review the possible mechanisms of MSCs in the treatment of DPN.

The 2019 American Diabetic Society guidelines recommend that flash glucose monitoring (FGM) can be used as a blood glucose monitoring method for adults with diabetes who need frequent blood glucose monitoring. Insulin pump therapy is an effective means for intensive treatment of diabetic patients. In order to adjust the dose flexibly and ensure safety, frequent blood glucose monitoring is needed. FGM has the advantages of showing the trend of blood glucose fluctuations, finding hidden high/hypoglycemia, adopting pre-factory calibration without finger blood correction, and wearing time of up to 14 days. When applied to insulin pump therapy, it can help patients improve their compliance with blood glucose monitoring, facilitate insulin pump dose adjustment and improve patients' self-management ability, which is conducive to improving blood glucose control. Among them, combining the glucose trend arrow and dynamic glucose map in FGM can more effectively display the law of blood glucose fluctuation, flexibly adjust the basal rate and large dose, reduce blood glucose fluctuation and reduce the occurrence of hypoglycemia. At the same time, pharmacoeconomic studies also show that FGM has good economic benefits for patients treated with intensive insulin therapy.